Cryptosporidium parvum is a coccidian parasite which infects intestinal and extraintestinal mucosal epithelium in humans, calves and other mammals. Cryptosporidiosis is a self-limiting diarrheal disease in hosts with normal immune systems; however, in immunocompromised patients such as those with AIDS, the disease is persistent and life threatening. AIDS patients are unable to mount a protective immune response against Cryptosporidium, thereby allowing the infection to persist. Endogenous autoinfective sporozoite and merozoite cycles contribute to persistent disease in these patients by maintaining the infection in the absence of re-exposure to an environmental source of Cryptosporidium. Control of the disease is further hampered by the absence of specific drugs effective against Cryptosporidium. Recent data indicate that antibody reactive with C. parvum sporozoite surface antigens can neutralize sporozoite infectivity and provide partial protection against cryptosporidiosis. Based on these data, this inter-institutional collaborative group hypothesizes that neutralizing antibodies reactive with sporozoite, merozoite and microgamete surface antigens can be used to prevent or treat cryptosporidiosis in immunodeficient hosts. This project will focus on developing neutralizing antibodies to the infective sporozoite stage. Antibodies will be targeted to neutralization-sensitive epitopes on the previously identified sporozoite surface antigens CPS-500, P-20 and P25-200. The University of Arizona and Utah State University projects will focus on developing neutralizing antibodies to the merozoite and sexual stages, respectively. To test the hypothesis, three specific aims will be completed: 1. Produce neutralizing monoclonal antibodies reactive with C. parvum sporozoite surface antigens CPS-500, P-20 and P25-200. 2. Determine if sporozoite neutralizing monoclonal antibodies can be used prophylactically to prevent infection by C. parvum oocyst-challenge. 3. Determine if sporozoite, merozoite and microgamete neutralizing monoclonal antibodies can be used therapeutically to terminate an existing C. parvum infection.